Variant 5-135033813-TGGCGGC-TGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2

The NM_002653.5(PITX1):c.66_68delGCC(p.Pro23del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000478 in 1,401,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

PITX1
NM_002653.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.71

Variant links:

Genes affected

PITX1 (HGNC:9004): (paired like homeodomain 1) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family are involved in organ development and left-right asymmetry. This protein acts as a transcriptional regulator involved in basal and hormone-regulated activity of prolactin. [provided by RefSeq, Jul 2008]

PITX1 links:

PITX1-AS1 (HGNC:48332): (PITX1 antisense RNA 1)

PITX1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002653.5. Strenght limited to Supporting due to length of the change: 1aa.

BS2

High AC in GnomAdExome4 at 67 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITX1	NM_002653.5 link	c.66_68delGCC	p.Pro23del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000265340.12	NP_002644.4	P78337X5D9A5
PITX1	XM_047417318.1 link	c.168_170delGCC	p.Pro57del	disruptive_inframe_deletion	Exon 2 of 4		XP_047273274.1
PITX1-AS1	NR_161235.1 link	n.267+286_267+288delGGC		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX1	ENST00000265340.12 link	c.66_68delGCC	p.Pro23del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_002653.5	ENSP00000265340.6		P78337

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000478

AC:

AN:

1401790

Hom.:

AF XY:

0.0000546

AC XY:

AN XY:

695550

show subpopulations

Gnomad4 AFR exome

AF:

0.0000340

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.0000809

Gnomad4 EAS exome

AF:

0.000169

Gnomad4 SAS exome

AF:

0.0000493

Gnomad4 FIN exome

AF:

0.000207

Gnomad4 NFE exome

AF:

0.0000257

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing